Biopolym. Cell. 2014; 30(6):413-425.
Nucleosomal packaging of eukaryotic DNA and regulation of transcription
1Golov A. K., 1, 2Razin S. V., 1Gavrilov A. A.
  1. Institute of Gene Biology, Russian Academy of Sciences
    34/5, Vavilova Str., Moscow, Russian Federation, 119334
  2. M. V. Lomonosov Moscow State University
    Leninskie Gory, 1/12, Moscow, Russian Federation, 119991


The eukaryotic nucleus harbors genomic DNA, which is tens of thousands of times greater in linear size than the nuclear diameter. Its high condensation is due to DNA packaging in chromatin, and DNA wrapping around nucleosomal globules is a key step in the process. A histone octamer, which forms the nucleosomal globule, interacts with DNA via electrostatic contacts. DNA–histone interactions are rather tight and prevent nucleosomal DNA from being accessed by various enzymes and transcription factors. At the same time, nucleosomes do not prevent transcription and other processes related to the genetic function of DNA. The review considers the structure and diversity of nucleosomes and the central role they play in regulating transcription. Special emphasis is placed on how internucleosomal interactions contribute to genome accessibility to transcription machinery and how nucleosomes are removed from regulatory elements and transcription units in a controlled manner during transcription elongation.
Keywords: chromatin, histone modifications, nucleosome, transcription


[1] Talbert PB, Ahmad K, Almouzni G, Ausi? J, Berger F, Bhalla PL, Bonner WM, Cande WZ, Chadwick BP, Chan SW, Cross GA, Cui L, Dimitrov SI, Doenecke D, Eirin-L?pez JM, Gorovsky MA, Hake SB, Hamkalo BA, Holec S, Jacobsen SE, Kamieniarz K, Khochbin S, Ladurner AG, Landsman D, Latham JA, Loppin B, Malik HS, Marzluff WF, Pehrson JR, Postberg J, Schneider R, Singh MB, Smith MM, Thompson E, Torres-Padilla ME, Tremethick DJ, Turner BM, Waterborg JH, Wollmann H, Yelagandula R, Zhu B, Henikoff S. A unified phylogeny-based nomenclature for histone variants. Epigenetics Chromatin. 2012;5:7.
[2] Simpson RT, Stafford DW. Structural features of a phased nucleosome core particle. Proc Natl Acad Sci U S A. 1983;80(1):51-5.
[3] Allfrey VG, Mirsky AE. Structural Modifications of Histones and their Possible Role in the Regulation of RNA Synthesis. Science. 1964;144(3618):559.
[4] Luger K, Richmond TJ. DNA binding within the nucleosome core. Curr Opin Struct Biol. 1998;8(1):33-40.
[5] Andrews AJ, Luger K. Nucleosome structure(s) and stability: variations on a theme. Annu Rev Biophys. 2011;40:99-117.
[6] Kornberg RD. Chromatin structure: a repeating unit of histones and DNA. Science. 1974;184(4139):868-71.
[7] Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. J Mol Biol. 2002;319(5):1097-113.
[8] van Holde KE. Chromatin. New York, Springer, 1989; 497 p. ttp://
[9] Bednar J, Horowitz RA, Grigoryev SA, Carruthers LM, Hansen JC, Koster AJ, Woodcock CL. Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proc Natl Acad Sci U S A. 1998;95(24):14173-8.
[10] Woodcock CL. Chromatin architecture. Curr Opin Struct Biol. 2006;16(2):213-20.
[11] Talbert PB, Henikoff S. Chromatin: packaging without nucleosomes. Curr Biol. 2012;22(24):R1040-3.
[12] Balhorn R. The protamine family of sperm nuclear proteins. Genome Biol. 2007;8(9):227.
[13] Suganuma T, Workman JL. Signals and combinatorial functions of histone modifications. Annu Rev Biochem. 2011;80:473-99.
[14] Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications. Biochim Biophys Acta. 2014;1839(8):627-43.
[15] Sidoli S, Cheng L, Jensen ON. Proteomics in chromatin biology and epigenetics: Elucidation of post-translational modifications of histone proteins by mass spectrometry. J Proteomics. 2012;75(12):3419-33.
[16] Zhang S, Roche K, Nasheuer HP, Lowndes NF. Modification of histones by sugar ?-N-acetylglucosamine (GlcNAc) occurs on multiple residues, including histone H3 serine 10, and is cell cycle-regulated. J Biol Chem. 2011;286(43):37483-95.
[17] Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, Lu Z, Ye Z, Zhu Q, Wysocka J, Ye Y, Khochbin S, Ren B, Zhao Y. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011;146(6):1016-28.
[18] Endoh M, Endo TA, Endoh T, Isono K, Sharif J, Ohara O, Toyoda T, Ito T, Eskeland R, Bickmore WA, Vidal M, Bernstein BE, Koseki H. Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity. PLoS Genet. 2012;8(7):e1002774.
[19] Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, Vakoc AL, Kim JE, Chen J, Lazar MA, Blobel GA, Vakoc CR. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Mol Cell Biol. 2008;28(8):2825-39.
[20] Brown DT, Alexander BT, Sittman DB. Differential effect of H1 variant overexpression on cell cycle progression and gene expression. Nucleic Acids Res. 1996;24(3):486-93.
[21] Jin C, Zang C, Wei G, Cui K, Peng W, Zhao K, Felsenfeld G. H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions. Nat Genet. 2009;41(8):941-5.
[22] Ioudinkova ES, Barat A, Pichugin A, Markova E, Sklyar I, Pirozhkova I, Robin C, Lipinski M, Ogryzko V, Vassetzky YS, Razin SV. Distinct distribution of ectopically expressed histone variants H2A.Bbd and MacroH2A in open and closed chromatin domains. PLoS One. 2012;7(10):e47157.
[23] Tolstorukov MY, Goldman JA, Gilbert C, Ogryzko V, Kingston RE, Park PJ. Histone variant H2A.Bbd is associated with active transcription and mRNA processing in human cells. Mol Cell. 2012;47(4):596-607.
[24] Talbert PB, Henikoff S. Histone variants--ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol. 2010;11(4):264-75.
[25] Finch JT, Klug A. Solenoidal model for superstructure in chromatin. Proc Natl Acad Sci U S A. 1976;73(6):1897-901.
[26] Li G, Reinberg D. Chromatin higher-order structures and gene regulation. Curr Opin Genet Dev. 2011;21(2):175-86.
[27] Woodcock CL, Frado LL, Rattner JB. The higher-order structure of chromatin: evidence for a helical ribbon arrangement. J Cell Biol. 1984;99(1 Pt 1):42-52.
[28] Dorigo B, Schalch T, Kulangara A, Duda S, Schroeder RR, Richmond TJ. Nucleosome arrays reveal the two-start organization of the chromatin fiber. Science. 2004;306(5701):1571-3.
[29] Schalch T, Duda S, Sargent DF, Richmond TJ. X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature. 2005;436(7047):138-41.
[30] van Holde K, Zlatanova J. Chromatin fiber structure: Where is the problem now? Semin Cell Dev Biol. 2007;18(5):651-8.
[31] Eltsov M, Maclellan KM, Maeshima K, Frangakis AS, Dubochet J. Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ. Proc Natl Acad Sci U S A. 2008;105(50):19732-7.
[32] Maeshima K, Hihara S, Takata H. New insight into the mitotic chromosome structure: irregular folding of nucleosome fibers without 30-nm chromatin structure. Cold Spring Harb Symp Quant Biol. 2010;75:439-44.
[33] Joti Y, Hikima T, Nishino Y, Kamada F, Hihara S, Takata H, Ishikawa T, Maeshima K. Chromosomes without a 30-nm chromatin fiber. Nucleus. 2012;3(5):404-10.
[34] Razin SV, Gavrilov AA. Chromatin without the 30-nm fiber: constrained disorder instead of hierarchical folding. Epigenetics. 2014;9(5):653-7. .
[35] Maeshima K, Imai R, Tamura S, Nozaki T. Chromatin as dynamic 10-nm fibers. Chromosoma. 2014;123(3):225-37.
[36] Rando OJ, Ahmad K. Rules and regulation in the primary structure of chromatin. Curr Opin Cell Biol. 2007;19(3):250-6.
[37] Campos EI, Reinberg D. Histones: annotating chromatin. Annu Rev Genet. 2009;43:559-99.
[38] Wang J, Zhuang J, Iyer S, Lin X, Whitfield TW, Greven MC, Pierce BG, Dong X, Kundaje A, Cheng Y, Rando OJ, Birney E, Myers RM, Noble WS, Snyder M, Weng Z. Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res. 2012;22(9):1798-812.
[39] Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, Garg K, John S, Sandstrom R, Bates D, Boatman L, Canfield TK, Diegel M, Dunn D, Ebersol AK, Frum T, Giste E, Johnson AK, Johnson EM, Kutyavin T, Lajoie B, Lee BK, Lee K, London D, Lotakis D, Neph S, Neri F, Nguyen ED, Qu H, Reynolds AP, Roach V, Safi A, Sanchez ME, Sanyal A, Shafer A, Simon JM, Song L, Vong S, Weaver M, Yan Y, Zhang Z, Zhang Z, Lenhard B, Tewari M, Dorschner MO, Hansen RS, Navas PA, Stamatoyannopoulos G, Iyer VR, Lieb JD, Sunyaev SR, Akey JM, Sabo PJ, Kaul R, Furey TS, Dekker J, Crawford GE, Stamatoyannopoulos JA. The accessible chromatin landscape of the human genome. Nature. 2012;489(7414):75-82.
[40] Elgin SC. DNAase I-hypersensitive sites of chromatin. Cell. 1981;27(3 Pt 2):413-5.
[41] Gross DS, Garrard WT. Nuclease hypersensitive sites in chromatin. Annu Rev Biochem. 1988;57:159-97.
[42] Felsenfeld G, Boyes J, Chung J, Clark D, Studitsky V. Chromatin structure and gene expression. Proc Natl Acad Sci U S A. 1996;93(18):9384-8.
[43] Boyle AP, Song L, Lee BK, London D, Keefe D, Birney E, Iyer VR, Crawford GE, Furey TS. High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells. Genome Res. 2011;21(3):456-64.
[44] John S, Sabo PJ, Thurman RE, Sung MH, Biddie SC, Johnson TA, Hager GL, Stamatoyannopoulos JA. Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat Genet. 2011;43(3):264-8.
[45] Kaplan T, Li XY, Sabo PJ, Thomas S, Stamatoyannopoulos JA, Biggin MD, Eisen MB. Quantitative models of the mechanisms that control genome-wide patterns of transcription factor binding during early Drosophila development. PLoS Genet. 2011;7(2):e1001290.
[46] Li XY, Thomas S, Sabo PJ, Eisen MB, Stamatoyannopoulos JA, Biggin MD. The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding. Genome Biol. 2011;12(4):R34.
[47] Pique-Regi R, Degner JF, Pai AA, Gaffney DJ, Gilad Y, Pritchard JK. Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data. Genome Res. 2011;21(3):447-55.
[48] Struhl K. Fundamentally different logic of gene regulation in eukaryotes and prokaryotes. Cell. 1999;98(1):1-4.
[49] Schnitzler GR. Control of nucleosome positions by DNA sequence and remodeling machines. Cell Biochem Biophys. 2008;51(2-3):67-80.
[50] Cairns BR. The logic of chromatin architecture and remodelling at promoters. Nature. 2009;461(7261):193-8.
[51] Mavrich TN, Ioshikhes IP, Venters BJ, Jiang C, Tomsho LP, Qi J, Schuster SC, Albert I, Pugh BF. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res. 2008;18(7):1073-83.
[52] Maier VK, Chioda M, Becker PB. ATP-dependent chromatosome remodeling. Biol Chem. 2008;389(4):345-52.
[53] Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem. 2009;78:273-304.
[54] Kaplan N, Moore IK, Fondufe-Mittendorf Y, Gossett AJ, Tillo D, Field Y, LeProust EM, Hughes TR, Lieb JD, Widom J, Segal E. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature. 2009;458(7236):362-6.
[55] Segal E, Widom J. Poly(dA:dT) tracts: major determinants of nucleosome organization. Curr Opin Struct Biol. 2009;19(1):65-71.
[56] Lee W, Tillo D, Bray N, Morse RH, Davis RW, Hughes TR, Nislow C. A high-resolution atlas of nucleosome occupancy in yeast. Nat Genet. 2007;39(10):1235-44.
[57] Struhl K. Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. Proc Natl Acad Sci U S A. 1985;82(24):8419-23.
[58] Badis G, Chan ET, van Bakel H, Pena-Castillo L, Tillo D, Tsui K, Carlson CD, Gossett AJ, Hasinoff MJ, Warren CL, Gebbia M, Talukder S, Yang A, Mnaimneh S, Terterov D, Coburn D, Li Yeo A, Yeo ZX, Clarke ND, Lieb JD, Ansari AZ, Nislow C, Hughes TR. A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell. 2008;32(6):878-87.
[59] Burd CJ, Archer TK. Chromatin architecture defines the glucocorticoid response. Mol Cell Endocrinol. 2013;380(1-2):25-31.
[60] Hartley PD, Madhani HD. Mechanisms that specify promoter nucleosome location and identity. Cell. 2009;137(3):445-58.
[61] Sherwood RI, Hashimoto T, O'Donnell CW, Lewis S, Barkal AA, van Hoff JP, Karun V, Jaakkola T, Gifford DK. Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape. Nat Biotechnol. 2014;32(2):171-8.
[62] Fascher KD, Schmitz J, H?rz W. Role of trans-activating proteins in the generation of active chromatin at the PHO5 promoter in S. cerevisiae. EMBO J. 1990;9(8):2523-8.
[63] Yudkovsky N, Logie C, Hahn S, Peterson CL. Recruitment of the SWI/SNF chromatin remodeling complex by transcriptional activators. Genes Dev. 1999;13(18):2369-74.
[64] Zaret KS, Carroll JS. Pioneer transcription factors: establishing competence for gene expression. Genes Dev. 2011;25(21):2227-41.
[65] Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJ. Comparative analysis of metazoan chromatin organization. Nature. 2014;512(7515):449-52.
[66] Shen Y, Yue F, McCleary DF, Ye Z, Edsall L, Kuan S, Wagner U, Dixon J, Lee L, Lobanenkov VV, Ren B. A map of the cis-regulatory sequences in the mouse genome. Nature. 2012;488(7409):116-20.
[67] Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dos? AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska-Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM 3rd, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, R?tsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X; modENCODE Consortium, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science. 2010;330(6012):1775-87.
[68] modENCODE Consortium, Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, Eaton ML, Landolin JM, Bristow CA, Ma L, Lin MF, Washietl S, Arshinoff BI, Ay F, Meyer PE, Robine N, Washington NL, Di Stefano L, Berezikov E, Brown CD, Candeias R, Carlson JW, Carr A, Jungreis I, Marbach D, Sealfon R, Tolstorukov MY, Will S, Alekseyenko AA, Artieri C, Booth BW, Brooks AN, Dai Q, Davis CA, Duff MO, Feng X, Gorchakov AA, Gu T, Henikoff JG, Kapranov P, Li R, MacAlpine HK, Malone J, Minoda A, Nordman J, Okamura K, Perry M, Powell SK, Riddle NC, Sakai A, Samsonova A, Sandler JE, Schwartz YB, Sher N, Spokony R, Sturgill D, van Baren M, Wan KH, Yang L, Yu C, Feingold E, Good P, Guyer M, Lowdon R, Ahmad K, Andrews J, Berger B, Brenner SE, Brent MR, Cherbas L, Elgin SC, Gingeras TR, Grossman R, Hoskins RA, Kaufman TC, Kent W, Kuroda MI, Orr-Weaver T, Perrimon N, Pirrotta V, Posakony JW, Ren B, Russell S, Cherbas P, Graveley BR, Lewis S, Micklem G, Oliver B, Park PJ, Celniker SE, Henikoff S, Karpen GH, Lai EC, MacAlpine DM, Stein LD, White KP, Kellis M. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science. 2010;330(6012):1787-97.
[69] Kasten M, Szerlong H, Erdjument-Bromage H, Tempst P, Werner M, Cairns BR. Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14. EMBO J. 2004;23(6):1348-59.
[70] VanDemark AP, Kasten MM, Ferris E, Heroux A, Hill CP, Cairns BR. Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation. Mol Cell. 2007;27(5):817-28.
[71] Chatterjee N, Sinha D, Lemma-Dechassa M, Tan S, Shogren-Knaak MA, Bartholomew B. Histone H3 tail acetylation modulates ATP-dependent remodeling through multiple mechanisms. Nucleic Acids Res. 2011;39(19):8378-91.
[72] Ferreira H, Flaus A, Owen-Hughes T. Histone modifications influence the action of Snf2 family remodelling enzymes by different mechanisms. J Mol Biol. 2007;374(3):563-79.
[73] Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev. 2000;64(2):435-59.
[74] Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41-5.
[75] Koutelou E, Hirsch CL, Dent SY. Multiple faces of the SAGA complex. Curr Opin Cell Biol. 2010;22(3):374-82.
[76] Albert I, Mavrich TN, Tomsho LP, Qi J, Zanton SJ, Schuster SC, Pugh BF. Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature. 2007;446(7135):572-6.
[77] Jin C, Felsenfeld G. Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes Dev. 2007;21(12):1519-29.
[78] Henikoff S. Nucleosome destabilization in the epigenetic regulation of gene expression. Nat Rev Genet. 2008;9(1):15-26.
[79] Mizuguchi G, Shen X, Landry J, Wu WH, Sen S, Wu C. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science. 2004;303(5656):343-8.
[80] Ruhl DD, Jin J, Cai Y, Swanson S, Florens L, Washburn MP, Conaway RC, Conaway JW, Chrivia JC. Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry. 2006;45(17):5671-7.
[81] Ranjan A, Mizuguchi G, FitzGerald PC, Wei D, Wang F, Huang Y, Luk E, Woodcock CL, Wu C. Nucleosome-free region dominates histone acetylation in targeting SWR1 to promoters for H2A.Z replacement. Cell. 2013;154(6):1232-45.
[82] Vermeulen M, Timmers HT. Grasping trimethylation of histone H3 at lysine 4. Epigenomics. 2010;2(3):395-406.
[83] Ng HH, Robert F, Young RA, Struhl K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell. 2003;11(3):709-19.
[84] Shilatifard A. The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis. Annu Rev Biochem. 2012;81:65-95.
[85] Jeronimo C, Bataille AR, Robert F. The writers, readers, and functions of the RNA polymerase II C-terminal domain code. Chem Rev. 2013;113(11):8491-522.
[86] Lee JH, Skalnik DG. CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex. J Biol Chem. 2005;280(50):41725-31.
[87] Thomson JP, Skene PJ, Selfridge J, Clouaire T, Guy J, Webb S, Kerr AR, Deaton A, Andrews R, James KD, Turner DJ, Illingworth R, Bird A. CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature. 2010;464(7291):1082-6.
[88] Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol. 2007;14(11):1025-40.
[89] Wysocka J, Swigut T, Xiao H, Milne TA, Kwon SY, Landry J, Kauer M, Tackett AJ, Chait BT, Badenhorst P, Wu C, Allis CD. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature. 2006;442(7098):86-90.
[90] Lee KK, Workman JL. Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol. 2007;8(4):284-95.
[91] ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57-74.
[92] Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet. 2006;7:29-59.
[93] Visel A, Rubin EM, Pennacchio LA. Genomic views of distant-acting enhancers. Nature. 2009;461(7261):199-205.
[94] Vavouri T, McEwen GK, Woolfe A, Gilks WR, Elgar G. Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet. 2006;22(1):5-10.
[95] Lettice LA, Heaney SJ, Purdie LA, Li L, de Beer P, Oostra BA, Goode D, Elgar G, Hill RE, de Graaff E. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet. 2003;12(14):1725-35.
[96] Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature. 2012;489(7414):109-13.
[97] Kikuta H, Laplante M, Navratilova P, Komisarczuk AZ, Engstr?m PG, Fredman D, Akalin A, Caccamo M, Sealy I, Howe K, Ghislain J, Pezeron G, Mourrain P, Ellingsen S, Oates AC, Thisse C, Thisse B, Foucher I, Adolf B, Geling A, Lenhard B, Becker TS. Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates. Genome Res. 2007;17(5):545-55.
[98] Birnbaum RY, Clowney EJ, Agamy O, Kim MJ, Zhao J, Yamanaka T, Pappalardo Z, Clarke SL, Wenger AM, Nguyen L, Gurrieri F, Everman DB, Schwartz CE, Birk OS, Bejerano G, Lomvardas S, Ahituv N. Coding exons function as tissue-specific enhancers of nearby genes. Genome Res. 2012;22(6):1059-68.
[99] Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature. 2009;459(7243):108-12.
[100] Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38(4):576-89.
[101] Calo E, Wysocka J. Modification of enhancer chromatin: what, how, and why? Mol Cell. 2013;49(5):825-37.
[102] Svotelis A, G?vry N, Gaudreau L. Regulation of gene expression and cellular proliferation by histone H2A.Z. Biochem Cell Biol. 2009;87(1):179-88.
[103] Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA, Boyer LA, Young RA, Jaenisch R. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010;107(50):21931-6.
[104] Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J. A unique chromatin signature uncovers early developmental enhancers in humans. Nature. 2011;470(7333):279-83.
[105] Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007;39(3):311-8.
[106] Phillips-Cremins JE, Corces VG. Chromatin insulators: linking genome organization to cellular function. Mol Cell. 2013;50(4):461-74.
[107] Schoborg T, Labrador M. Expanding the roles of chromatin insulators in nuclear architecture, chromatin organization and genome function. Cell Mol Life Sci. 2014;71(21):4089-113.
[108] Ulianov SV, Markova EN, Gavrilov AA, Razin SV. Insulators in vertebrates: regulatory mechanisms and chromatin structure. Biopolym Cell. 2012; 28(4):252-60.
[109] Kirkland JG, Raab JR, Kamakaka RT. TFIIIC bound DNA elements in nuclear organization and insulation. Biochim Biophys Acta. 2013;1829(3-4):418-24.
[110] Van Bortle K, Corces VG. tDNA insulators and the emerging role of TFIIIC in genome organization. Transcription. 2012;3(6):277-84.
[111] Ong CT, Corces VG. CTCF: an architectural protein bridging genome topology and function. Nat Rev Genet. 2014;15(4):234-46.
[112] Holwerda SJ, de Laat W. CTCF: the protein, the binding partners, the binding sites and their chromatin loops. Philos Trans R Soc Lond B Biol Sci. 2013;368(1620):20120369.
[113] Kyrchanova O, Georgiev P. Chromatin insulators and long-distance interactions in Drosophila. FEBS Lett. 2014;588(1):8-14.
[114] Gurudatta BV, Corces VG. Chromatin insulators: lessons from the fly. Brief Funct Genomic Proteomic. 2009;8(4):276-82.
[115] Ernst J, Kellis M. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol. 2010;28(8):817-25.
[116] Wendt KS, Yoshida K, Itoh T, Bando M, Koch B, Schirghuber E, Tsutsumi S, Nagae G, Ishihara K, Mishiro T, Yahata K, Imamoto F, Aburatani H, Nakao M, Imamoto N, Maeshima K, Shirahige K, Peters JM. Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature. 2008;451(7180):796-801.
[117] Hon G, Wang W, Ren B. Discovery and annotation of functional chromatin signatures in the human genome. PLoS Comput Biol. 2009;5(11):e1000566.
[118] Raab JR, Kamakaka RT. Insulators and promoters: closer than we think. Nat Rev Genet. 2010;11(6):439-46.
[119] De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK, Muller H, Ragoussis J, Wei CL, Natoli G. A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 2010;8(5):e1000384.
[120] Koch F, Fenouil R, Gut M, Cauchy P, Albert TK, Zacarias-Cabeza J, Spicuglia S, de la Chapelle AL, Heidemann M, Hintermair C, Eick D, Gut I, Ferrier P, Andrau JC. Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Nat Struct Mol Biol. 2011;18(8):956-63.
[121] Pekowska A, Benoukraf T, Zacarias-Cabeza J, Belhocine M, Koch F, Holota H, Imbert J, Andrau JC, Ferrier P, Spicuglia S. H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J. 2011;30(20):4198-210.
[122] Koch F, Andrau JC. Initiating RNA polymerase II and TIPs as hallmarks of enhancer activity and tissue-specificity. Transcription. 2011;2(6):263-8.
[123] Natoli G, Andrau JC. Noncoding transcription at enhancers: general principles and functional models. Annu Rev Genet. 2012;46:1-19.
[124] Kireeva ML, Walter W, Tchernajenko V, Bondarenko V, Kashlev M, Studitsky VM. Nucleosome remodeling induced by RNA polymerase II: loss of the H2A/H2B dimer during transcription. Mol Cell. 2002;9(3):541-52.
[125] Izban MG, Luse DS. Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing. Genes Dev. 1991;5(4):683-96.
[126] Singh J, Padgett RA. Rates of in situ transcription and splicing in large human genes. Nat Struct Mol Biol. 2009;16(11):1128-33.
[127] Selth LA, Sigurdsson S, Svejstrup JQ. Transcript Elongation by RNA Polymerase II. Annu Rev Biochem. 2010;79:271-93.
[128] Smolle M, Workman JL. Transcription-associated histone modifications and cryptic transcription. Biochim Biophys Acta. 2013;1829(1):84-97.
[129] Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science. 2003;301(5636):1090-3.
[130] Thiriet C, Hayes JJ. Replication-independent core histone dynamics at transcriptionally active loci in vivo. Genes Dev. 2005;19(6):677-82.
[131] Jamai A, Imoberdorf RM, Strubin M. Continuous histone H2B and transcription-dependent histone H3 exchange in yeast cells outside of replication. Mol Cell. 2007;25(3):345-55.
[132] Dion MF, Kaplan T, Kim M, Buratowski S, Friedman N, Rando OJ. Dynamics of replication-independent histone turnover in budding yeast. Science. 2007;315(5817):1405-8.
[133] Rufiange A, Jacques PE, Bhat W, Robert F, Nourani A. Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1. Mol Cell. 2007;27(3):393-405.
[134] Adkins MW, Tyler JK. The histone chaperone Asf1p mediates global chromatin disassembly in vivo. J Biol Chem. 2004;279(50):52069-74.
[135] Schwabish MA, Struhl K. Asf1 mediates histone eviction and deposition during elongation by RNA polymerase II. Mol Cell. 2006;22(3):415-22.
[136] Walfridsson J, Khorosjutina O, Matikainen P, Gustafsson CM, Ekwall K. A genome-wide role for CHD remodelling factors and Nap1 in nucleosome disassembly. EMBO J. 2007;26(12):2868-79.
[137] Robinson KM, Schultz MC. Replication-independent assembly of nucleosome arrays in a novel yeast chromatin reconstitution system involves antisilencing factor Asf1p and chromodomain protein Chd1p. Mol Cell Biol. 2003;23(22):7937-46.
[138] Zlatanova J, Seebart C, Tomschik M. Nap1: taking a closer look at a juggler protein of extraordinary skills. FASEB J. 2007;21(7):1294-310.
[139] Kuryan BG, Kim J, Tran NN, Lombardo SR, Venkatesh S, Workman JL, Carey M. Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro. Proc Natl Acad Sci U S A. 2012;109(6):1931-6.
[140] Wittschieben BO, Otero G, de Bizemont T, Fellows J, Erdjument-Bromage H, Ohba R, Li Y, Allis CD, Tempst P, Svejstrup JQ. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Mol Cell. 1999;4(1):123-8.
[141] Cho H, Orphanides G, Sun X, Yang XJ, Ogryzko V, Lees E, Nakatani Y, Reinberg D. A human RNA polymerase II complex containing factors that modify chromatin structure. Mol Cell Biol. 1998;18(9):5355-63.
[142] Govind CK, Zhang F, Qiu H, Hofmeyer K, Hinnebusch AG. Gcn5 promotes acetylation, eviction, and methylation of nucleosomes in transcribed coding regions. Mol Cell. 2007;25(1):31-42.
[143] Ginsburg DS, Govind CK, Hinnebusch AG. NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5. Mol Cell Biol. 2009;29(24):6473-87.
[144] Kaplan CD, Laprade L, Winston F. Transcription elongation factors repress transcription initiation from cryptic sites. Science. 2003;301(5636):1096-9.
[145] Cheung V, Chua G, Batada NN, Landry CR, Michnick SW, Hughes TR, Winston F. Chromatin- and transcription-related factors repress transcription from within coding regions throughout the Saccharomyces cerevisiae genome. PLoS Biol. 2008;6(11):e277.
[146] Li B, Gogol M, Carey M, Lee D, Seidel C, Workman JL. Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science. 2007;316(5827):1050-4.
[147] Silva AC, Xu X, Kim HS, Fillingham J, Kislinger T, Mennella TA, Keogh MC. The replication-independent histone H3-H4 chaperones HIR, ASF1, and RTT106 co-operate to maintain promoter fidelity. J Biol Chem. 2012;287(3):1709-18.
[148] Gkikopoulos T, Schofield P, Singh V, Pinskaya M, Mellor J, Smolle M, Workman JL, Barton GJ, Owen-Hughes T. A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome organization. Science. 2011;333(6050):1758-60.
[149] Hennig BP, Bendrin K, Zhou Y, Fischer T. Chd1 chromatin remodelers maintain nucleosome organization and repress cryptic transcription. EMBO Rep. 2012;13(11):997-1003.
[150] Pointner J, Persson J, Prasad P, Norman-Axelsson U, Str?lfors A, Khorosjutina O, Krietenstein N, Svensson JP, Ekwall K, Korber P. CHD1 remodelers regulate nucleosome spacing in vitro and align nucleosomal arrays over gene coding regions in S. pombe. EMBO J. 2012;31(23):4388-403.
[151] Shim YS, Choi Y, Kang K, Cho K, Oh S, Lee J, Grewal SI, Lee D. Hrp3 controls nucleosome positioning to suppress non-coding transcription in eu- and heterochromatin. EMBO J. 2012;31(23):4375-87.
[152] Govind CK, Qiu H, Ginsburg DS, Ruan C, Hofmeyer K, Hu C, Swaminathan V, Workman JL, Li B, Hinnebusch AG. Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes. Mol Cell. 2010;39(2):234-46.
[153] Drouin S, Laram?e L, Jacques P?, Forest A, Bergeron M, Robert F. DSIF and RNA polymerase II CTD phosphorylation coordinate the recruitment of Rpd3S to actively transcribed genes. PLoS Genet. 2010;6(10):e1001173.
[154] Krogan NJ, Kim M, Tong A, Golshani A, Cagney G, Canadien V, Richards DP, Beattie BK, Emili A, Boone C, Shilatifard A, Buratowski S, Greenblatt J. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol. 2003;23(12):4207-18.
[155] Li B, Howe L, Anderson S, Yates JR 3rd, Workman JL. The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II. J Biol Chem. 2003;278(11):8897-903.
[156] Bannister AJ, Schneider R, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T. Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes. J Biol Chem. 2005;280(18):17732-6.
[157] Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007;448(7153):553-60.
[158] Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, Peterson CL. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science. 2006;311(5762):844-7.
[159] Robinson PJ, An W, Routh A, Martino F, Chapman L, Roeder RG, Rhodes D. 30 nm chromatin fibre decompaction requires both H4-K16 acetylation and linker histone eviction. J Mol Biol. 2008;381(4):816-25.
[160] Allahverdi A, Yang R, Korolev N, Fan Y, Davey CA, Liu CF, Nordenski?ld L. The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association. Nucleic Acids Res. 2011;39(5):1680-91.
[161] Pepenella S, Murphy KJ, Hayes JJ. Intra- and inter-nucleosome interactions of the core histone tail domains in higher-order chromatin structure. Chromosoma. 2014;123(1-2):3-13.
[162] Zhou J, Fan JY, Rangasamy D, Tremethick DJ. The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression. Nat Struct Mol Biol. 2007;14(11):1070-6.
[163] Greaves IK, Rangasamy D, Ridgway P, Tremethick DJ. H2A.Z contributes to the unique 3D structure of the centromere. Proc Natl Acad Sci U S A. 2007;104(2):525-30.
[164] Fan JY, Rangasamy D, Luger K, Tremethick DJ. H2A.Z alters the nucleosome surface to promote HP1alpha-mediated chromatin fiber folding. Mol Cell. 2004;16(4):655-61.
[165] Heitz E. Der Nachweis der Chromosomen. Z Bot. 1928;18: 625-81.
[166] Zeng W, Ball AR Jr, Yokomori K. HP1: heterochromatin binding proteins working the genome. Epigenetics. 2010;5(4):287-92.
[167] Kueng S, Oppikofer M, Gasser SM. SIR proteins and the assembly of silent chromatin in budding yeast. Annu Rev Genet. 2013;47:275-306.
[168] Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature. 2001;410(6824):116-20.
[169] Canzio D, Chang EY, Shankar S, Kuchenbecker KM, Simon MD, Madhani HD, Narlikar GJ, Al-Sady B. Chromodomain-mediated oligomerization of HP1 suggests a nucleosome-bridging mechanism for heterochromatin assembly. Mol Cell. 2011;41(1):67-81.
[170] Fritsch L, Robin P, Mathieu JR, Souidi M, Hinaux H, Rougeulle C, Harel-Bellan A, Ameyar-Zazoua M, Ait-Si-Ali S. A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol Cell. 2010;37(1):46-56.
[171] Schotta G, Ebert A, Krauss V, Fischer A, Hoffmann J, Rea S, Jenuwein T, Dorn R, Reuter G. Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 2002;21(5):1121-31.
[172] Groner AC, Meylan S, Ciuffi A, Zangger N, Ambrosini G, D?nervaud N, Bucher P, Trono D. KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading. PLoS Genet. 2010;6(3):e1000869.
[173] Mateos-Langerak J, Brink MC, Luijsterburg MS, van der Kraan I, van Driel R, Verschure PJ. Pericentromeric heterochromatin domains are maintained without accumulation of HP1. Mol Biol Cell. 2007;18(4):1464-71.
[174] Velichko AK, Kantidze OL, Razin SV. HP1? is not necessary for the structural maintenance of centromeric heterochromatin. Epigenetics. 2011;6(3):380-7.
[175] Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, Kohlmaier A, Opravil S, Tachibana M, Shinkai Y, Martens JH, Jenuwein T. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell. 2003;12(6):1577-89.
[176] Hawkins RD, Hon GC, Lee LK, Ngo Q, Lister R, Pelizzola M, Edsall LE, Kuan S, Luu Y, Klugman S, Antosiewicz-Bourget J, Ye Z, Espinoza C, Agarwahl S, Shen L, Ruotti V, Wang W, Stewart R, Thomson JA, Ecker JR, Ren B. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell. 2010;6(5):479-91.
[177] Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet. 2009;41(2):246-50.
[178] Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature. 2011;469(7330):343-9.
[179] Butenko Y, Ohad N. Polycomb-group mediated epigenetic mechanisms through plant evolution. Biochim Biophys Acta. 2011;1809(8):395-406.
[180] Di Croce L, Helin K. Transcriptional regulation by Polycomb group proteins. Nat Struct Mol Biol. 2013;20(10):1147-55.
[181] Schwartz YB, Kahn TG, Nix DA, Li XY, Bourgon R, Biggin M, Pirrotta V. Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet. 2006;38(6):700-5.
[182] Tolhuis B, de Wit E, Muijrers I, Teunissen H, Talhout W, van Steensel B, van Lohuizen M. Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nat Genet. 2006;38(6):694-9.
[183] N?gre N, Hennetin J, Sun LV, Lavrov S, Bellis M, White KP, Cavalli G. Chromosomal distribution of PcG proteins during Drosophila development. PLoS Biol. 2006;4(6):e170.
[184] Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet. 2008;4(10):e1000242.
[185] Lynch MD, Smith AJ, De Gobbi M, Flenley M, Hughes JR, Vernimmen D, Ayyub H, Sharpe JA, Sloane-Stanley JA, Sutherland L, Meek S, Burdon T, Gibbons RJ, Garrick D, Higgs DR. An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. EMBO J. 2012;31(2):317-29.
[186] Cui K, Zang C, Roh TY, Schones DE, Childs RW, Peng W, Zhao K. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell. 2009;4(1):80-93.
[187] K?hler C, Villar CB. Programming of gene expression by Polycomb group proteins. Trends Cell Biol. 2008;18(5):236-43.
[188] Francis NJ, Kingston RE, Woodcock CL. Chromatin compaction by a polycomb group protein complex. Science. 2004;306(5701):1574-7.
[189] Simon JA, Kingston RE. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol. 2009;10(10):697-708.
[190] Bantignies F, Cavalli G. Polycomb group proteins: repression in 3D. Trends Genet. 2011;27(11):454-64.
[191] Chen L, Widom J. Mechanism of transcriptional silencing in yeast. Cell. 2005;120(1):37-48.
[192] Sha K, Gu SG, Pantalena-Filho LC, Goh A, Fleenor J, Blanchard D, Krishna C, Fire A. Distributed probing of chromatin structure in vivo reveals pervasive chromatin accessibility for expressed and non-expressed genes during tissue differentiation in C. elegans. BMC Genomics. 2010;11:465.
[193] Filion GJ, van Bemmel JG, Braunschweig U, Talhout W, Kind J, Ward LD, Brugman W, de Castro IJ, Kerkhoven RM, Bussemaker HJ, van Steensel B. Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell. 2010;143(2):212-24.
[194] Verschure PJ, van der Kraan I, Manders EM, Hoogstraten D, Houtsmuller AB, van Driel R. Condensed chromatin domains in the mammalian nucleus are accessible to large macromolecules. EMBO Rep. 2003;4(9):861-6.
[195] G?risch SM, Lichter P, Rippe K. Mobility of multi-subunit complexes in the nucleus: accessibility and dynamics of chromatin subcompartments. Histochem Cell Biol. 2005;123(3):217-28.
[196] Pack C, Saito K, Tamura M, Kinjo M. Microenvironment and effect of energy depletion in the nucleus analyzed by mobility of multiple oligomeric EGFPs. Biophys J. 2006;91(10):3921-36.
[197] Hihara S, Pack CG, Kaizu K, Tani T, Hanafusa T, Nozaki T, Takemoto S, Yoshimi T, Yokota H, Imamoto N, Sako Y, Kinjo M, Takahashi K, Nagai T, Maeshima K. Local nucleosome dynamics facilitate chromatin accessibility in living mammalian cells. Cell Rep. 2012;2(6):1645-56.
[198] Piacentini L, Fanti L, Negri R, Del Vescovo V, Fatica A, Altieri F, Pimpinelli S. Heterochromatin protein 1 (HP1a) positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila. PLoS Genet. 2009;5(10):e1000670.
[199] Riddle NC, Minoda A, Kharchenko PV, Alekseyenko AA, Schwartz YB, Tolstorukov MY, Gorchakov AA, Jaffe JD, Kennedy C, Linder-Basso D, Peach SE, Shanower G, Zheng H, Kuroda MI, Pirrotta V, Park PJ, Elgin SC, Karpen GH. Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res. 2011;21(2):147-63.
[200] Brookes E, de Santiago I, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, Stock JK, Heidemann M, Eick D, Nozaki N, Kimura H, Ragoussis J, Teichmann SA, Pombo A. Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell. 2012;10(2):157-70.
[201] Kanhere A, Viiri K, Ara?jo CC, Rasaiyaah J, Bouwman RD, Whyte WA, Pereira CF, Brookes E, Walker K, Bell GW, Pombo A, Fisher AG, Young RA, Jenner RG. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol Cell. 2010;38(5):675-88.
[202] Enderle D, Beisel C, Stadler MB, Gerstung M, Athri P, Paro R. Polycomb preferentially targets stalled promoters of coding and noncoding transcripts. Genome Res. 2011;21(2):216-26.
[203] B?hler M, Gasser SM. Silent chromatin at the middle and ends: lessons from yeasts. EMBO J. 2009;28(15):2149-61.
[204] Towbin BD, Gonzalez-Sandoval A, Gasser SM. Mechanisms of heterochromatin subnuclear localization. Trends Biochem Sci. 2013;38(7):356-63.
[205] Stock JK, Giadrossi S, Casanova M, Brookes E, Vidal M, Koseki H, Brockdorff N, Fisher AG, Pombo A. Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat Cell Biol. 2007;9(12):1428-35.
[206] Taddei A, Van Houwe G, Nagai S, Erb I, van Nimwegen E, Gasser SM. The functional importance of telomere clustering: global changes in gene expression result from SIR factor dispersion. Genome Res. 2009;19(4):611-25.
[207] Padeken J, Heun P. Nucleolus and nuclear periphery: velcro for heterochromatin. Curr Opin Cell Biol. 2014;28:54-60.
[208] Pinheiro I, Margueron R, Shukeir N, Eisold M, Fritzsch C, Richter FM, Mittler G, Genoud C, Goyama S, Kurokawa M, Son J, Reinberg D, Lachner M, Jenuwein T. Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell. 2012;150(5):948-60.
[209] Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science. 2002;295(5558):1306-11.
[210] de Wit E, de Laat W. A decade of 3C technologies: insights into nuclear organization. Genes Dev. 2012;26(1):11-24.
[211] Gavrilov AA, Razin SV, Iarovaia OV. C-methods to study 3D organization of the eukaryotic genome. Biopolym Cell. 2012; 28(4):245-51.